Adiponectin Cardioprotection After Myocardial Ischemia/Reperfusion Involves the Reduction of Oxidative/Nitrative Stress

Author:

Tao Ling1,Gao Erhe1,Jiao Xiangying1,Yuan Yuexing1,Li Shuzhuang1,Christopher Theodore A.1,Lopez Bernard L.1,Koch Walter1,Chan Lawrence1,Goldstein Barry J.1,Ma Xin L.1

Affiliation:

1. From the Department of Emergency Medicine (L.T., X.J., Y.Y., S.L., T.A.C., B.L.P., X.L.M.), Center for Translational Medicine (E.G., W.K.), and Division of Endocrinology, Diabetes, and Metabolic Diseases (B.J.G.), Thomas Jefferson University, Philadelphia, Pa; and Section of Diabetes, Endocrinology, and Metabolism (L.C.), Department of Medicine, Baylor College of Medicine, Houston, Tex.

Abstract

Background— Several clinical studies have demonstrated that levels of adiponectin are significantly reduced in patients with type 2 diabetes and that adiponectin levels are inversely related to the risk of myocardial ischemia. The present study was designed to determine the mechanism by which adiponectin exerts its protective effects against myocardial ischemia/reperfusion. Methods and Results— Adiponectin −/− or wild-type mice were subjected to 30 minutes of myocardial ischemia followed by 3 hours or 24 hours (infarct size and cardiac function) of reperfusion. Myocardial infarct size and apoptosis, production of peroxynitrite, nitric oxide (NO) and superoxide, and inducible NO synthase (iNOS) and gp91 phox protein expression were compared. Myocardial apoptosis and infarct size were markedly enhanced in adiponectin −/− mice ( P <0.01). Formation of NO, superoxide, and their cytotoxic reaction product, peroxynitrite, were all significantly higher in cardiac tissue obtained from adiponectin −/− than from wild-type mice ( P <0.01). Moreover, myocardial ischemia/reperfusion–induced iNOS and gp91 phox protein expression was further enhanced, but endothelial NOS phosphorylation was reduced in cardiac tissue from adiponectin −/− mice. Administration of the globular domain of adiponectin 10 minutes before reperfusion reduced myocardial ischemia/reperfusion–induced iNOS/gp91 phox protein expression, decreased NO/superoxide production, blocked peroxynitrite formation, and reversed proapoptotic and infarct-enlargement effects observed in adiponectin −/− mice. Conclusion— The present study demonstrates that adiponectin is a natural molecule that protects hearts from ischemia/reperfusion injury by inhibition of iNOS and nicotinamide adenine dinucleotide phosphate-oxidase protein expression and resultant oxidative/nitrative stress.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine

Cited by 404 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3